Objective To investigate the effects of Huoxueqiwei granules on the expressions of eNOS,nNOS and Cx43 in the rats with VC and ED,and explore its mechanism in the treatment of VC and ED.Methods A total of 120 SD rats were divided into the normal group,the sham group,the model group,and low-,medium-,and high-dose Huoxueqiwei granule groups.A rat model of VC and ED was established through Turner's method and APO test.APO tests were performed to detect erectile function on the 1st,3rd,and 8th weekend;the diameter of the left spermatic vein was measured before and after intervention;Levels of serum FSH,LH,FT,and TT were detected by ELISA;The ultrastructure of penile tissue was observed using a transmission electron microscope;The mRNA expressions of nNOS and eNOS in penile were analyzed by RT-PCR;The expression of Cx43 in penile was detected by western blot.Results After modeling,the width of the left spermatic vein in the model group and each treatment group was increased significantly(P<0.01).After intervention,the vein width in each treatment group was decreased(P<0.05).For the first APO test,there was no difference in the erectile function of rats in each group(P>0.05).For the second APO test,the erectile function of rats in the model group and each treatment group was decreased significantly(P<0.01).For the third APO test,the erectile function of rats in each treatment group was recovered(P<0.05).The levels of FSH and LH in the model group were increased(P<0.05),while the levels of TT and FT were decreased(P<0.05).Levels of serum FSH and LH in the medium and high dose groups were all decreased(P<0.05),while levels of TT and FT were increased(P<0.05).The mRNA expressions of eNOS and nNOS in penis were significantly downregulated(P<0.01)in the model group.The mRNA expressions of eNOS and nNOS in the penis of each treatment group were significantly upregulated(P<0.01).Cx43 protein level was significantly decreased(P<0.01)in the model group,and its level in each treatment group was significantly increased(P<0.01).The structure of CCSMC in each treatment group was intact,and in a small number of fields,the collagen fiber structure and mitochondria were restored,the number of endoplasmic reticulum was increased.Conclusions Huoxueqiwei granules not only improve varicocele and sex hormone levels,but also upregulate eNOS,nNOS and Cx43 expressions in the corpus cavernosum of the penis,which thereby enhances the erectile function of rats.